This is a multifaceted, multidisciplinary, interdepartmental and coordinated investigation to obtain a better understanding of the etiology, pathogenesis and to explore possible improved therapeutic approaches which might be applied to small cell carcinoma of the lung in man. It is proposed to continue and expand a spectrum of studies which will lead to a better understanding of the basic pathobiology of the putative cell of origin and the tumor and to develop an experimental model of this disease. Long-term cultures of the human tumor have been established already and are currently available for a wide variety of experimental studies. Studies on the growth of these tumors in nude mice and use for various therapeutic protocols is planned. Since small cell cultures produce a wide variety of peptide as well as steroid hormones, it is proposed to study the regulatory factors which are involved in the synthesis and secretion of these hormones as compared with normal cells. The use of long-term cultures of activated T cells as the means of modifying experimental leukemia in mice has led to our proposing that a comparable immunological study should involve small cell carcinoma as a analogous solid tumor. It is proposed to evaluate certain parameters in patients, e.g., cell kinetics which then would be compared to the cells from the same tumor that would be established in culture and those which would be grown in nude mice. It is also planned to evaluate a certain limited number of hormones, particularly "big" ACTH, as tumor markers, and relate these values to tumor mass in patients throughout the clinical course, and particularly in relationship to therapeutic response. In addition, it is proposed to evaluate chromosomal abnormalities, which are associated with these tumors, and the persistence or alterations that may occur with time.